Ethyl Acetate → 1-(1,3-dioxolan-2-ylmethyl)-7-methoxypyrido(2,3-b)pyrazin-2(1H)-one

Temperature

85 °C

To a suspension of 4.0 g of 7-bromopyrido(2,3-b)pyrazin-2(1H)-one in 40 mL of N,N-dimethylformamide, 8.2 g of a 28% sodium methoxide/methanol solution and 0.25 g of copper (I) bromide were added at room temperature, and the mixture was stirred at 80 to 90° C. for 3 hours under a nitrogen atmosphere. The reaction mixture was cooled to 55° C., thereto was added 2.8 mL of 2-bromomethyl-1,3-dioxolan, and the mixture was stirred at 80 to 90° C. for 1 hour 30 minutes under a nitrogen atmosphere. The reaction mixture was cooled to room temperature and then left overnight. The mixture was further stirred at 80 to 90° C. for 1 hour, and then stirred at 90 to 100° C. for 1 hour 30 minutes. The reaction mixture was cooled to room temperature, and then ethyl acetate and water were added thereto. The insoluble substance was filtered off, the organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The organic layer and the extract were combined, the resultant solution was dried over anhydrous magnesium sulfate, and the solvent was then distilled off under reduced pressure. The resultant residue was purified by flash silica gel column chromatography using gradient elution with chloroform:methanol=100:0 to 95:5, ethyl acetate was added to the orange oily substance thus obtained, and the solid was filtered off to obtain 0.12 g of 1-(1,3-dioxolan-2-ylmethyl)-7-methoxypyrido(2,3-b)pyrazin-2(1H)-one as an orange solid.

1. additionwere added at room temperature
2. temperatureThe reaction mixture was cooled to 55° C.
3. stirringthe mixture was stirred at 80 to 90° C. for 1 hour 30 minutes under a nitrogen atmosphere
4. temperatureThe reaction mixture was cooled to room temperature
5. waitleft overnight
6. stirringThe mixture was further stirred at 80 to 90° C. for 1 hour
7. stirringstirred at 90 to 100° C. for 1 hour 30 minutes
8. temperatureThe reaction mixture was cooled to room temperature
9. filtrationThe insoluble substance was filtered off
10. customthe organic layer was separated
11. extractionthe aqueous layer was extracted with ethyl acetate
12. dry with materialthe resultant solution was dried over anhydrous magnesium sulfate
13. distillationthe solvent was then distilled off under reduced pressure
14. customThe resultant residue was purified by flash silica gel column chromatography
15. washelution with chloroform
16. additionmethanol=100:0 to 95:5, ethyl acetate was added to the orange oily substance
17. customthus obtained
18. filtrationthe solid was filtered off

ORD record

ord-84c31800e98545a59d8fe35830d238a4

Source dataset

uspto-grants-2013_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08367831B2